前额叶皮质
内分泌学
内科学
氧化应激
尼氏体
NMDA受体
海马结构
海马体
谷氨酸受体
谷氨酸的
化学
心理学
医学
神经科学
受体
病理
染色
认知
作者
Jelena Martinović,Marina Zarić Kontić,Milorad Dragić,Ana Todorović,Ivana Stojanović,Nataša Mitrović,Ivana Grković,Dunja Drakulić
标识
DOI:10.1016/j.bbr.2022.114072
摘要
D-galactose (d-gal) is broadly used in animal aging studies as its chronic administration mimics learning and memory impairments related to aging in humans. However, within the few studies that utilize chronic oral d-gal intake, none of them is focused on alteration in synaptic structure and function. We examined the effects of 6-weeks oral d-gal intake (200 mg/kg and 500 mg/kg, dissolved in tap water) on age-related changes, with emphasis on the prefrontal cortex (PFC) and hippocampus (HIP) of adult male Wistar rats. Memory assessment was followed by histological examination of the PFC and HIP (Nissl staining and Iba-1 immunostaining), while in crude synaptosomal fractions the state of oxidative stress and the expression of proteins involved in glutamatergic signaling was determined. Although applied dosages compromised memory, alterations such as impaired sensory-motor function and aberrant morphology were not detected. In the PFC, analysis of microglia revealed reduction of branching pattern following d-gal intake, in parallel with increased oxidative damage of proteins, lipids and disturbed pro-oxidant antioxidant balance. These changes in the PFC were further accompanied with decreased levels of vesicular glutamate transporter 1, syntaxin-1 and NMDA receptor 2B subunit in both treated groups. Simultaneously, the increased hippocampal oxidative damage of lipids was detected. Results indicate successful provocation of age-related changes following oral d-gal intake, and suggest greater sensitivity of the PFC to d-gal treatment than HIP.
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